Effects of the tetronic acid derivatives AO33 (losigamone) and AO78 on epileptiform activity and on stimulus-induced calcium concentration changes in rat hippocampal slices.
The effects of members of a new class of anticonvulsants, the tetronic acid derivatives, were studied in 3 in vitro models of epileptogenesis in rat hippocampal slices; the picrotoxin, the low magnesium and the low calcium model. The effects of AO33 (losigamone) and AO78 on stimulus-induced decreases in extracellular calcium concentration were also investigated. In all 3 models of epileptogenesis, both drugs blocked spontaneous and reduced stimulus-induced epileptiform discharges dose dependently and reversibly. Stimulus-induced changes in [Ca2+]0 were markedly diminished by these agents. The fact that the tetronic acid derivatives block the low Ca seizure-like events which develop independently from chemical synaptic transmission suggests that these agents have non-synaptic or direct membrane actions with subsequently reduced cellular excitability.
Köhr
G
G
Institut für Neurophysiologie, Universität zu Köln, Cologne, F.R.G.
Heinemann
U
U
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D005110:Extracellular Space / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D009994:Osmolar Concentration; D010852:Picrotoxin; D051381:Rats; D013569:Synapses / Q000378:metabolism
D002118:Calcium; D005663:Furans; D008274:Magnesium; D010852:Picrotoxin; C065426:A 078; C065427:losigame